Naphthoquinone enhances antigen-related airway inflammation in mice

Abstract

ABSTRACT:The current authors have previously demonstrated that diesel exhaust particles (DEP) enhance antigen-related airway inflammation in mice. Furthermore, a recent study has shown that organic chemicals in DEP, rather than their carbonaceous nuclei, are important contributors to the aggravating effects of airway inflammation. However, the components in DEP responsible for the enhancing effects on the model remain to be identified.The current authors investigated the effects of naphthoquinone (NQ), one of the extractable chemical compounds of DEP, on antigen-related airway inflammation, local expression of cytokine proteins, and antigen-specific immunoglobulin (Ig) production in mice. Pulmonary exposure to NQ dose-dependently aggravated antigen-related airway inflammation, as characterised by infiltration of eosinophils and lymphocytes around the airways and an increase in goblet cells in the bronchial epithelium. Combined exposure to NQ and antigen enhanced the local expression of interleukin (IL)-4, IL-5, eotaxin, macrophage chemoattractant protein-1 and keratinocyte chemoattractant, compared with exposure to antigen or NQ alone. Also, NQ exhibited adjuvant activity for the antigen-specific production of IgG 1 and IgG 2a .These results provide the first experimental evidence that naphthoquinone can enhance antigen-related airway inflammation in vivo, and that naphthoquinone can, to some extent, partly play a role in the pathogenesis of diesel exhaust particle toxicity on the condition. DEP are complicated particles consisting of carbonaceous nuclei and a vast number of organic chemical compounds such as polyaromatic hydrocarbons, aliphatic hydrocarbons, heterocycles, and quinones. Previous studies have indicated that organic chemicals extracted from DEP result in induction of apoptosis [11], increase oxidative stress [12], and induce the production of inflammatory cells [13][14][15] through the release of pro-inflammatory molecules in vitro [15,16]. The current authors have recently demonstrated that extracted organic chemicals from DEP, rather than residual carbonaceous nuclei of DEP after extraction, predominantly enhance antigen-related airway inflammation in mice [17]. However, detailed studies concerning the component(s) of DEP responsible for their effects on the respiratory system and/or pulmonary diseases remain unsatisfied, which is particularly the case for in vivo studies.A variety of quinones have been identified as DEP components [18,19]. Quinones themselves have toxicological properties, serving as alkylating agents and interacting with, for example, flavoproteins to generate reactive oxygen species (ROS) which can induce biological injury [20][21][22][23]. Phenanthraquinone (PQ) is one of the quinones contained in DEP [19,23]. The current authors have recently shown that PQ induces recruitment of inflammatory cells, such as eosinophils and neutrophils, into the lung with the lung expression of pro-inflammatory molecules such as interleukin (IL)-5 and eotaxin in vivo [24]. More recently, it h...

Chemical Knockdown of Protein-tyrosine Phosphatase 1B by 1,2-Naphthoquinone through Covalent Modification Causes Persistent Transactivation of Epidermal Growth Factor Receptor

“…In other studies, 1,2-NQ has been shown to cause the contraction of tracheal smooth muscle in the same concentration range, through activation of the EGFR system (19) leading ultimately to stimulation of the vanillin receptor to cause smooth muscle contraction. In vivo experiments in which 1,2-NQ was intratracheally administered to ovalbumin-sensitized mice resulted in enhanced airway sensitivity and goblet cell hyperplasia, two actions that may indicate airway hyper-responsiveness that is associated with lung disease (12). Because these tissue and whole animal responses are occurring at comparable concentrations, it appears likely that the in vivo effects are mediated by initial inactivation of PTP1B.…”

Inert 50-nm Polystyrene Nanoparticles That Modify Pulmonary Dendritic Cell Function and Inhibit Allergic Airway Inflammation

“…Carbon black ultrafine particles and carbon nanotubes (9,13,14) contain significant concentrations of organic or metallic impurities that can themselves promote pulmonary inflammation (15,16). Diesel exhaust particles consist of a range of particle sizes from the nanoscale up to 10 mm and contain aromatic hydrocarbon contaminants that can directly promote lung inflammation (6,7,17). Titanium dioxide nanoparticles and carbon nanotubes can additionally promote lung inflammation by inducing pulmonary oxidative stress in vivo (13,18).…”

“…Studies have also shown that carbon black nanoparticles (9)(10)(11), titanium dioxide nanoparticles (12), and carbon nanotubes (13,14) can promote allergic sensitization, allergic airway inflammation (AAI), and/or stimulate dendritic cell (DC) and allergen-specific T cells. However, a significant component of these particle adjuvant effects has been attributed to adsorbed toxic chemicals and metallic impurities and the ability to induce oxidative stress (6,7,13,(15)(16)(17)(18)(19). Notably, information regarding the long-term effects of inert, nontoxic and noninflammatory nanoparticles delivered into the lung on asthma development and pulmonary DC distribution and function is lacking.…”

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“…In particular, exposure to ambient environmental pollutants is known to be associated several allergic symptoms. For example, experimental evidence has shown that exposure to diesel exhaust particles (Inoue et al, 2007;Liu et al, 2008) and phthalate (Yanagisawa et al, 2008) increase allergic responses, and these pollutants have adjuvant activity.…”